The Wellcome Trust has boosted the value of its fund to almost £25.9 billion despite "choppier markets" and pledged around £900 million a year in charitable spending until at least 2022.
Britain's biggest charity and medical research institute said it notched up a total return of 13.4% for the year to September 30, or 10.7% after inflation.
It made pre-tax net income of £2.2 billion, flat on the previous year.
The group - the main source of non-Governmental biomedical research in the UK - said it has now returned 11.7% on average on its investments in the 10 years since the financial crisis.
It said its performance means it can vow to spend around £900 million a year on average until 2022 from its primary fund, which covers most of its charitable activities.
Another £200 million will also be made available for priority areas and other large-scale, high-impact activities such as drug resistant infections and mental health, it added.
But the trust cautioned investment returns recorded since the 2008 financial crisis will not continue.
Nick Moakes, chief investment officer and managing partner of the investment division at Wellcome, added: "As the global economic cycle matures, markets have become more volatile.
"Our global focus and long-term horizon have helped us navigate a choppier environment.
"The decade since the global financial crisis has seen very strong investment returns, which we do not expect to be repeated over the next 10 years."
In its annual report, the group said its spending on charities over the year to September 30 fell sharply to £723 million from £1.2 billion in 2016-17 but it said this was largely down to the timing of significant spending commitments.
Trust chairwoman Baroness Manningham-Buller said: "I am pleased to report that, once again, our investments have done well.
"The performance of our portfolio in more difficult global markets has provided the ability for us to increase our charitable commitment over the last 10 years.
"Our sincere thanks go to the investment team for the part that they have played in making this possible."
The organisation was set up in 1936.
It was launched after the death of pharmaceutical entrepreneur Sir Henry Wellcome, who left the entire share capital of his company to trustees charged with spending income to further human and animal health.
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